Molecular Mechanisms of Insulin Resistance Development

Insulin resistance (IR) is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The developm...

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Autores principales:	Vsevolod Arsen'evich Tkachuk, Alexander Vyacheslavovich Vorotnikov
Formato:	article
Lenguaje:	EN RU
Publicado:	Endocrinology Research Centre 2014
Materias:	insulin resistance type 2 diabetes mellitus insulin-dependent intracellular signaling feedback irs protein phosphor?ylation Nutritional diseases. Deficiency diseases RC620-627
Acceso en línea:	https://doaj.org/article/b241062810944dc19909e8bbc4ce26cf
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spelling	oai:doaj.org-article:b241062810944dc19909e8bbc4ce26cf2021-11-14T09:00:19ZMolecular Mechanisms of Insulin Resistance Development2072-03512072-037810.14341/DM2014229-40https://doaj.org/article/b241062810944dc19909e8bbc4ce26cf2014-07-01T00:00:00Zhttps://www.dia-endojournals.ru/jour/article/view/6597https://doaj.org/toc/2072-0351https://doaj.org/toc/2072-0378Insulin resistance (IR) is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion. IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell). Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades. This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.Vsevolod Arsen'evich TkachukAlexander Vyacheslavovich VorotnikovEndocrinology Research Centrearticleinsulin resistancetype 2 diabetes mellitusinsulin-dependent intracellular signalingfeedbackirs proteinphosphor?ylationNutritional diseases. Deficiency diseasesRC620-627ENRUСахарный диабет, Vol 17, Iss 2, Pp 29-40 (2014)
institution	DOAJ
collection	DOAJ
language	EN RU
topic	insulin resistance type 2 diabetes mellitus insulin-dependent intracellular signaling feedback irs protein phosphor?ylation Nutritional diseases. Deficiency diseases RC620-627
spellingShingle	insulin resistance type 2 diabetes mellitus insulin-dependent intracellular signaling feedback irs protein phosphor?ylation Nutritional diseases. Deficiency diseases RC620-627 Vsevolod Arsen'evich Tkachuk Alexander Vyacheslavovich Vorotnikov Molecular Mechanisms of Insulin Resistance Development
description	Insulin resistance (IR) is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM) and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion. IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell). Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades. This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.
format	article
author	Vsevolod Arsen'evich Tkachuk Alexander Vyacheslavovich Vorotnikov
author_facet	Vsevolod Arsen'evich Tkachuk Alexander Vyacheslavovich Vorotnikov
author_sort	Vsevolod Arsen'evich Tkachuk
title	Molecular Mechanisms of Insulin Resistance Development
title_short	Molecular Mechanisms of Insulin Resistance Development
title_full	Molecular Mechanisms of Insulin Resistance Development
title_fullStr	Molecular Mechanisms of Insulin Resistance Development
title_full_unstemmed	Molecular Mechanisms of Insulin Resistance Development
title_sort	molecular mechanisms of insulin resistance development
publisher	Endocrinology Research Centre
publishDate	2014
url	https://doaj.org/article/b241062810944dc19909e8bbc4ce26cf
work_keys_str_mv	AT vsevolodarsenevichtkachuk molecularmechanismsofinsulinresistancedevelopment AT alexandervyacheslavovichvorotnikov molecularmechanismsofinsulinresistancedevelopment
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Molecular Mechanisms of Insulin Resistance Development

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